Induced abortion incidence and associated factors in a cohort of women living with HIV in Rio De Janeiro, Brazil, 1996-2016.

BACKGROUND: Abortion is a public health problem in Latin America and is more common among women living with HIV. OBJECTIVE: to verify the incidence and factors associated with induced abortion in a cohort of women living with HIV assisted in a reference service for care for individuals with HIV/AIDS in Rio de Janeiro/Brazil. METHODS: Prospective cohort during the period 1996-2016. We estimated the incidence of induced abortions during follow-up in the cohort by calculating person-time incidence rates [per 100 persons-years (PY)] and investigated the factors associated with the outcome "induced abortion" using a generalized linear mixed model. RESULTS: 753 women and 210 pregnancies were included in the present analysis. We estimated an induced abortion incidence rate of 0.68/100 persons-years (95% confidence interval [CI]: 0.47; 0.94) in the study period, with a significant reduction after 2006. The main factors associated with an induced abortion were currently living with a partner (adjusted OR [AdjOR] 0.32 95% CI: 0.10-0.98), number of children (2 children AdjOR 0.12, 95% CI: 0.02-0.95) and the type of antiretroviral treatment used (regimen without Efavirenz: AdjOR: 0.11, 95% CI 0.02-0.70). CONCLUSIONS: We showed a significant reduction in the incidence of induced abortions in a cohort of women living with HIV in Rio de Janeiro, Brazil, probably due to a decrease in the incidence of pregnancies observed in the same period. The factors associated with a lower occurrence of induced abortion suggest a good integration between the clinical and reproductive assistance offered to those women.

Bacterial sexually transmitted infections among men who have sex with men and transgender women using oral pre-exposure prophylaxis in Latin America (ImPrEP): a secondary analysis of a prospective, open-label, multicentre study.

BACKGROUND: The global burden of sexually transmitted infections (STIs) poses a challenge in the context of HIV pre-exposure prophylaxis (PrEP) programmes. We aimed to explore factors associated with prevalent, incident, and recurrent STIs in men who have sex with men (MSM) and transgender women on PrEP in Brazil, Mexico, and Peru. METHODS: ImPrEP was a prospective, single-arm, open-label, multicentre study that enrolled MSM and transgender women in the context of the public health systems of Brazil (14 sites), Mexico (four sites), and Peru (ten sites) between February, 2018, and June, 2021. Eligibility criteria followed regional PrEP guidelines at the study start, including participants aged 18 years and older, not living with HIV, and reporting at least one of the following in the previous 6 months: condomless anal sex (CAS), anal sex with partner(s) living with HIV, any bacterial STI, or transactional sex. Eligible participants were screened and enrolled on the same day to receive daily oral PrEP (tenofovir disoproxil fumarate 300 mg and emtricitabine 200 mg). We assessed three outcomes: prevalent bacterial STIs, incident bacterial STIs, and recurrent bacterial STIs. Testing occurred at baseline and quarterly for syphilis, anorectal chlamydia, and anorectal gonorrhoea. Behavioural data were collected at baseline and quarterly. The study was registered with the Brazilian Registry of Clinical Trials, U1111-1217-6021. FINDINGS: Among all 9509 participants included in the ImPrEP study (3928 [41·3%] in Brazil, 3288 [34·6%] in Mexico, and 2293 [24·1%] in Peru), 8525 (89·7%) had available STI results at baseline and were included in the prevalent STI analysis, and 7558 (79·5%) had available STI results during follow-up and were included in the incident and recurrent STI analyses. 2184 (25·6%) of 8525 participants had any bacterial STI at baseline. STI incidence during follow-up was 31·7 cases per 100 person-years (95% CI 30·7-32·7), with the highest rate for anorectal chlamydia (11·6 cases per 100 person-years, 95% CI 11·0-12·2), followed by syphilis (10·5 cases per 100 person-years, 9·9-11·1) and anorectal gonorrhoea (9·7 cases per 100 person-years, 9·2-10·3). Although only 2391 (31·6%) of 7558 participants had at least one STI during follow-up, 915 (12·1%) participants had recurrent diagnoses, representing 2328 (61·2%) of 3804 incident STI diagnoses. Characteristics associated with prevalent, incident, and recurrent STIs included younger age, multiple sex partners, receptive CAS, substance use, and previous STI diagnoses at baseline (incident or recurrent only). INTERPRETATION: Our findings underscore the nuanced dynamics of STI transmission among MSM and transgender women across Latin America, highlighting an urgent need for tailored interventions to mitigate STI burden effectively, especially among the most susceptible individuals. FUNDING: Unitaid, WHO, and ministries of health (Brazil, Mexico, and Peru). TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

A Cluster of Diutina catenulata Funguria in Patients with Coronavirus Disease 2019 (COVID-19) Hospitalized in a Tertiary Reference Hospital from Rio de Janeiro, Brazil.

During the COVID-19 pandemic, fungal infections, especially pulmonary aspergillosis, mucormycosis, and invasive candidiasis, have emerged as a significant health concern. Beyond Candida albicans, the most common cause of invasive candidiasis, other rare ascomycetous yeast species have been described in tertiary care units, potentially posing a broader health threat. We have isolated, from September 2020 to June 2021, nine Diutina catenulata strains from urine samples of six patients. This was intriguing as this fungus had not been previously identified in our institution, nor after June 2021. Therefore, we decided to outline the clinical features of the patients with this rare pathogen, to describe phenotypic characteristics, including antifungal susceptibility profiles, of this yeast species and to identify the genetic makeup through whole-genome sequencing analysis to evaluate if this was a cluster of genetically similar D. catenulata isolates in our institution. The strains were identified through MALDI-TOF MS analyses and Sanger sequencing of two rDNA regions. All patients yielding D. catenulata from urine samples needed ventilator support and used urinary catheters during hospitalization for treatment of COVID-19. None of them had received COVID-19 vaccines. Morphological and biochemical profiles of the nine strains were largely consistent, although fluconazole susceptibility varied, ranging from 4 to 32 µg/mL. Phylogenomic analysis revealed minimal genetic variation among the isolates, with low intrapopulation variation, supported by the identification of only 84 SNPs across all strains. Therefore, we propose that the yeast strains isolated were part of a cluster of D. catenulata funguria in the context of COVID-19.

Association Between SARS-CoV-2 Viral Load and COVID-19 Vaccination in 4 Phase 3 Trials.

Coronavirus disease 2019 (COVID-19) vaccines reduce severe disease and mortality and may lessen transmission, measured by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL). Evaluating vaccine associations in VL at COVID-19 diagnosis in 4 phase 3 randomized, placebo-controlled vaccine trials, July 2020 to July 2021, VL reductions were 2.78 log10 copies/mL (95% confidence interval [CI], 1.38-4.18; n = 60 placebo, 11 vaccine) and 2.12 log10 copies/mL (95% CI, 1.44-2.80; n = 594 placebo, 36 vaccine) for NVX-CoV2373 and mRNA-1273, respectively. Associations were not significant for AZD1222 (0.59 log10 copies/mL; 95% CI, -.19 to 1.36; n = 90 placebo, 78 vaccine) or Ad26.COV2.S (0.23 log10 copies/mL; 95% CI, -.01 to .47; n = 916 placebo, 424 vaccine). Thus, vaccines potentially decreased transmission when ancestral SARS-CoV-2 predominated. Clinical Trials Registration. NCT04470427, NCT04505722, NCT04516746, NCT04611802.

HIV-1 controllers exhibit an enhanced antiretroviral innate state characterised by overexpression of p21 and MCPIP1 and silencing of ERVK-6 RNA expression.

BACKGROUND: Human immunodeficiency virus (HIV)-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWHs) who naturally control HIV-1 replication and overexpress some cellular restriction factors that negatively regulate the LTR-driven transcription of HIV-1 proviruses. OBJECTIVES: To understand the ability of HICs to control the expression of endogenous retroviruses. METHODS: We measured endogenous retrovirus type K6 (ERVK-6) RNA expression in peripheral blood mononuclear cells (PBMCs) of HICs (n = 23), antiretroviral (ART)-suppressed subjects (n = 8), and HIV-1-negative (NEG) individuals (n = 10) and correlated the transcript expression of ERVK-6 with multiple HIV-1 cellular restriction factors. FINDINGS: Our study revealed that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with that in both the ART and NEG control groups. Moreover, we detected that ERVK-6 RNA levels in PBMCs across all groups were negatively correlated with the expression levels of p21 and MCPIP1, two cellular restriction factors that limit the activation of macrophages and T cells by downregulating the activity of NF-kB. MAIN CONCLUSIONS: These findings support the hypothesis that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both exogenous (HIV-1) and endogenous (ERVK-6) retroviruses. Future studies with larger cohorts should be performed to confirm this hypothesis and to explore the role of p21 and MCPIP1 in regulating HERV-K expression in physiological and pathological conditions.

Impact of Covid-19 pandemic on HIV testing, recent infections and annualized incidence among cisgender men who have sex with men and transgender women in Brazil.

BACKGROUND: The Covid-19 pandemic had great impact on HIV care and prevention worldwide, including in Brazil. We compared HIV testing, recent infection, and annualized incidence according to Covid-19 pandemic period among men who have sex with men (MSM) and transgender women (TGW). SETTING: HIV/STI testing, prevention and treatment referral service in Rio de Janeiro, Brazil. METHODS: We used Maxim HIV-1 Limiting Antigen Avidity EIA as part of recent infection testing algorithm to identify recent HIV infections and estimate annualized HIV incidences in pre- (March/2018-February/2020) and post-Covid-19 pandemic onset period (March/2020-January 2022). Multivariable logistic regression model assessed factors associated with recent HIV infection. RESULTS: Among 4590 MSM and TGW, 593 (12.9%) tested positive for HIV and 119 (2.6%) were identified as having recent infection. Percentage of recent HIV infection did not differ between Covid-19 periods. Overall annualized HIV incidence rates were 6.0% (95%CI:4.2-7.7) and 6.6% (95%CI:4.3-9.0) in pre- and post-Covid-19 periods, respectively. During the post-Covid-19 period, higher incidence rates were observed among TGW (8.4%[95%CI:2.9-13.9]), those aged 18-24 years (7.8%[ 95%CI:4.0-11.7]), Black race (7.9%[95%CI:3.8-12.0]), and with <12 years of schooling (7.8%[95%CI:4.8-10.8]). Incidence rates were significantly higher in the post-Covid-19 period for those aged>30 years and TGW, and lower for those with more years of schooling. CONCLUSION: HIV incidence estimates remain high among MSM and TGW in Brazil, especially among the most vulnerable. The consequences of the Covid-19 pandemic on the HIV epidemic will likely persist and contribute to worsening HIV outcomes.

Mpox, sexually transmitted infections and combination prevention: insights from a major cohort in Rio de Janeiro, Brazil.

OBJECTIVE: To evaluate the prevalence and characteristics of concurrent bacterial sexually transmitted infections (bSTIs) among individuals with mpox. DESIGN: Prospective cohort study of participants aged 18 years or older with confirmed mpox conducted in Rio de Janeiro, Brazil. This cross-sectional analysis includes only participants who underwent bSTI testing at baseline between June 2022 and January 2024. METHODS: Participants were offered testing for chlamydia/gonorrhea (NAAT, anorectal swabs) and syphilis (active diagnosis if VDRL ≥ 1/8). Baseline prevalence of bSTIs was calculated, and participant characteristics were described based on concomitant bSTI diagnosis (yes/no). Chi-squared/Fisher's tests were used for qualitative variables, and the Wilcoxon rank-sum test for quantitative variables. RESULTS: Out of 634 enrolled participants, 538 (84.9%) were tested for STIs and included in this analysis, mostly cisgender men, aged 30-39 years with postsecondary education. Overall prevalence of concomitant bSTI was 37.3%, mainly syphilis, followed by chlamydia and gonorrhea. Half of the participants were living with HIV, and one third was on HIV pre-exposure prophylaxis. Concomitant bSTI diagnosis at the time of mpox assessment was associated with being aged 30-39 years, self-identifying as cisgender men, having HIV-positive status, reporting proctitis symptoms and reporting any STI in the past 12 months. CONCLUSIONS: Our data reveals a notable prevalence of concomitant bSTIs among participants with confirmed mpox at a prominent infectious diseases' referral center in Rio de Janeiro, Brazil. These findings underscore the importance of integrating mpox into the differential diagnosis of anogenital manifestations and the promotion of combination prevention strategies within sexual healthcare services.

Anti-PF4 positivity and platelet activation after Ad26.COV2·S vaccination in Brazil.

INTRODUCTION: The Ad26.COV2·S (Janssen/Johnson & Johnson) COVID-19 vaccine, has been rarely associated with vaccine-induced immune thrombocytopenia and thrombosis (VITT). We investigated the prevalence of anti-PF4 antibody positivity, thrombocytopenia, D-dimer elevation, plasmatic thromboinflammatory markers, and platelet functional assays following Ad26.COV2·S vaccination in Rio de Janeiro, Brazil. METHODS: From July to September 2021, participants were assessed prior, 1, and 3 weeks post-vaccination. Platelet count and D-dimer were measured at each visit and anti-PF4 at week 3. A positive anti-PF4 prompted retrospective testing of the sample from week 0. Individuals with new thrombocytopenia or elevated D-dimer, positive anti-PF4, and 38 matched controls without laboratory abnormalities were evaluated for plasmatic p-selectin, tissue factor, and functional platelet activation assays. RESULTS: 630 individuals were included; 306 (48.57%) females, median age 28 years. Forty-two (6.67%) presented ≥1 laboratory abnormality in week 1 or 3. Five (0.79%) had thrombocytopenia, 31 (4.91%) elevated D-dimer, and 9 (1.57%) had positive anti-PF4 at week 3. Individuals with laboratory abnormalities and controls showed a slight increase in plasmatic p-selectin and tissue factor. Ten individuals with laboratory abnormalities yielded increased surface expression of p-selectin, and their ability to activate platelets in a FcγRIIa dependent manner was further evaluated. Two were partially inhibited by high concentrations of heparin and blockage of FcγRII with IV.3 antibody. Plasma obtained before vaccination produced similar results, suggesting a lack of association with vaccination. CONCLUSIONS: Vaccination with Ad26.COV2·S vaccine led to a very low frequency of low-titer positive anti-PF4 antibodies, elevation of D-dimer, and mild thrombocytopenia, with no associated clinically relevant increase in thromboinflammatory markers and platelet activation.

Exploring the Resurgence of a Neglected Disease: Lessons From the 2023-2024 Mpox Outbreak in Rio de Janeiro, Brazil.

Following the 2022 global mpox outbreak, diagnoses decreased worldwide, even in settings with limited vaccine access. In 2023-2024, a new outbreak emerged in Rio de Janeiro, Brazil, highlighting the importance of continuous surveillance, preventive measures such as vaccination in vulnerable populations, and treatment options, emphasizing equitable global health technology distribution.

The rising tide of HIV among young men who have sex with men in Brazil: insights from the Conectad@s study.

Background: Young gay, bisexual, and other men who have sex with men (YMSM) in Latin America experience disproportionately high rates of HIV. While new case numbers have stabilised in other demographics, the incidence of HIV in this particular group continues to rise. We estimated the prevalence of HIV and sexually transmitted infections (STI) and identified correlates of new HIV diagnoses among YMSM in Brazil. Methods: Conectad@s was a respondent-driven sampling-based study to recruit and engage YMSM in HIV prevention and treatment services in Rio de Janeiro, Brazil (November 2021-October 2022). Eligibility criteria were age 18-24 years and self-identification as MSM (cis/trans) or non-binary person who have sex with men. Participants underwent HIV/STI testing and completed a socio-behavioural questionnaire. We described baseline characteristics by HIV status and used logistic regression models to identify correlates of new HIV diagnoses. Trial ID: DERR1-10.2196/34885. Findings: Among 409 participants, 370 (90.5%) self-identified as cisgender men, nine (2.2%) transgender men, and 30 (7.3%) non-binary. Median age was 21 years (IQR: 20-23), with 80 (19.6%) aged 18-19 years. Most self-identified as Black or Pardo (70.6%); 109 (26.7%) never tested for HIV. HIV prevalence was 9.8%; 50% (n = 20/40) were newly diagnosed with HIV. Only nine participants ever used PrEP and three were currently using it. Overall, 133 (32.5%) reported sexual violence in their lifetime and 102 (24.9%) reported a suicide attempt. Prevalence of active syphilis, chlamydia, and gonorrhoea were 14.4%, 15.9%, and 14.7%, respectively. New HIV diagnoses were positively associated with engaging in high-risk behaviour (aOR 4.88 [95% CI: 1.88-13.40]) and anxiety (aOR 2.67 [95% CI: 1.01-7.70]), and negatively associated with ever disclosing sexual orientation (aOR 0.19 [95% CI: 0.04-0.92]) and HIV knowledge (aOR 0.77 [95% CI: 0.59-1.01]). Interpretation: High prevalence of HIV coupled with a high proportion of new HIV diagnoses underscore a potentially growing HIV epidemic among YMSM in Brazil. Funding: National Institutes of Health (NIH), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Ministry of Health of Brazil.

Evaluation of Xpert point-of-care assays for detection of HIV infection in persons using long-acting cabotegravir for pre-exposure prophylaxis.

Detection of HIV infection may be challenging in persons using long-acting cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) due to viral suppression and reduced/delayed antibody production. We evaluated two point-of-care tests for detecting HIV infection in persons who received CAB-LA in the HPTN 083 trial. Samples were obtained from 12 participants who received CAB-LA and had delayed detection of HIV infection using HIV rapid tests and an antigen/antibody test (52 plasma samples; 18 dried blood spot [DBS] samples). Plasma samples were tested with the Xpert HIV-1 Viral Load XC test (Xpert VL-XC); DBS samples were tested with the total nucleic acid Xpert HIV-1 Qual XC test (Xpert Qual-XC). Results from these assays were compared to results from three reference, laboratory-based, plasma RNA assays (Aptima HIV-1 Qualitative assay [Aptima Qual]; Aptima HIV-1 Quant DX Assay [Aptima Quant]; cobas HIV-1/HIV-2 Qualitative Test [cobas]). HIV RNA was detected with all four plasma assays for all samples with viral loads (VLs) ≥ 200 copies/mL; the number of samples with VLs < 200 copies/mL with HIV RNA detected was: Xpert VL-XC: 19/26 (73.1%); Aptima Qual: 17/26 (65.4%); Aptima Quant: 17/26 (65.4%); and cobas: 12/21 (57.1%). The Xpert Qual-XC assay was positive for all DBS samples with VLs ≥ 200 copies/mL and 1/10 DBS with VLs < 200 copies/mL. The performance of the Xpert VL-XC assay was comparable to the reference assays for detecting HIV infection in these cases. The Xpert Qual-XC assay was less sensitive than plasma-based HIV RNA assays for detecting HIV in the setting of CAB-LA PrEP. IMPORTANCE: HIV RNA assays can detect HIV infections earlier than HIV rapid tests or Ag/Ab tests in persons using CAB-LA PrEP. Earlier HIV diagnosis could allow for earlier treatment initiation and reduced risk of INSTI resistance. POC tests may help detect HIV infection before CAB-LA administration and may be more accessible than laboratory-based assays in some settings. In this study, the POC Xpert VL-XC assay detected HIV RNA in most samples from individuals who received CAB-LA PrEP and had delayed detection of HIV infection with HIV rapid tests and an Ag/Ab test. The performance of this assay was similar to laboratory-based HIV RNA assays in this cohort. The POC Xpert Qual-XC assay detects both HIV RNA and DNA, with a higher viral load cutoff for RNA detection. This assay was negative for most lower viral load samples and did not offer an advantage for HIV screening in persons using CAB-LA PrEP.

SARS-CoV-2 transmission in a highly vulnerable population of Brazil: a household cohort study.

Background: Household transmission studies seek to understand the transmission dynamics of a pathogen by estimating the risk of infection from household contacts and community exposures. We estimated within/extra-household SARS-CoV-2 infection risk and associated factors in a household cohort study in one of the most vulnerable neighbourhoods in Rio de Janeiro city. Methods: Individuals ≥1 years-old with suspected or confirmed COVID-19 in the past 30 days (index cases) and household members aged ≥1 year were enrolled and followed at 14 and 28 days (study period November/2020-December/2021). RT-PCR testing, COVID-19 symptoms, and SARS-CoV-2 serologies were ascertained in all visits. Chain binomial household transmission models were fitted using data from 2024 individuals (593 households). Findings: Extra-household infection risk was 74.2% (95% credible interval [CrI] 70.3-77.8), while within-household infection risk was 11.4% (95% CrI 5.7-17.2). Participants reporting having received two doses of a COVID-19 vaccine had lower extra-household (68.9%, 95% CrI 57.3-77.6) and within-household (4.1%, 95% CrI 0.4-16.6) infection risk. Within-household infection risk was higher among participants aged 10-19 years, from overcrowded households, and with low family income. Contrastingly, extra-household infection risk was higher among participants aged 20-29 years, unemployed, and public transportation users. Interpretation: Our study provides important insights into COVID-19 household/community transmission in a vulnerable population that resided in overcrowded households and who struggled to adhere to lockdown policies and social distancing measures. The high extra-household infection risk highlights the extreme social vulnerability of this population. Prioritising vaccination of the most socially vulnerable could protect these individuals and reduce widespread community transmission. Funding: Fundação Oswaldo Cruz, CNPq, FAPERJ, Royal Society, Instituto Serrapilheira, FAPESP.

Patterns of Diversity and Humoral Immunogenicity for HIV-1 Antisense Protein (ASP).

HIV-1 has an antisense gene overlapping env that encodes the ASP protein. ASP functions are still unknown, but it has been associated with gp120 in the viral envelope and membrane of infected cells, making it a potential target for immune response. Despite this, immune response patterns against ASP are poorly described and can be influenced by the high genetic variability of the env gene. To explore this, we analyzed 100k HIV-1 ASP sequences from the Los Alamos HIV sequence database using phylogenetic, Shannon entropy (Hs), and logo tools to study ASP variability in worldwide and Brazilian sequences from the most prevalent HIV-1 subtypes in Brazil (B, C, and F1). Data obtained in silico guided the design and synthesis of 15-mer overlapping peptides through spot synthesis on cellulose membranes. Peptide arrays were screened to assess IgG and IgM responses in pooled plasma samples from HIV controllers and individuals with acute or recent HIV infection. Excluding regions with low alignment accuracy, several sites with higher variability (Hs > 1.5) were identified among the datasets (25 for worldwide sequences, 20 for Brazilian sequences). Among sites with Hs < 1.5, sequence logos allowed the identification of 23 other sites with subtype-specific signatures. Altogether, amino acid variations with frequencies > 20% in the 48 variable sites identified were included in 92 peptides, divided into 15 sets, representing near full-length ASP. During the immune screening, the strongest responses were observed in three sets, one in the middle and one at the C-terminus of the protein. While some sets presented variations potentially associated with epitope displacement between IgG and IgM targets and subtype-specific signatures appeared to impact the level of response for some peptides, signals of cross-reactivity were observed for some sets despite the presence of B/C/F1 signatures. Our data provides a map of ASP regions preferentially targeted by IgG and IgM responses. Despite B/C/F1 subtype signatures in ASP, the amino acid variation in some areas preferentially targeted by IgM and IgG did not negatively impact the response against regions with higher immunogenicity.

Evaluation of the analytical and clinical performance of the Abbott Alinity m instrument for the quantification of HIV-1 RNA plasma viral load in a reference laboratory in Rio de Janeiro, Brazil.

OBJECTIVES: We sought to evaluate the analytical performance of the Alinity m system (Abbott Molecular) and to compare the clinical performance of HIV-1 assays on the Alinity m and m2000 RealTime platforms (Abbott Molecular). METHODS: The sensitivity, precision, and accuracy of the Alinity m instrument were determined using a panel of standard samples (n = 46). The carryover effect was assessed by analyzing HIV-negative clinical samples (n = 20). Clinical performance of the Alinity m and m2000 RealTime platforms was compared using surplus HIV-positive patient plasma samples (n = 39). RESULTS: The Alinity m HIV-1 assay demonstrated 100% sensitivity, a high precision (coefficient of variation (s/x̄) × 100 ≤1.5% [SD ≤ 0.05] logarithm to base 10 [log10] copies/mL), and partial accuracy over the quantification range. Analysis of clinical samples suggested that the Alinity m HIV-1 assay does not cause carryover effect and produced a mean bias of 0.209 log10 copies/mL (95% CI, 0.153-0.265) compared with the m2000 RealTime System. CONCLUSIONS: The Alinity m instrument's performance correlated to that of the m2000 RealTime platform and showed excellent sensitivity, precision, and accuracy, despite producing overquantification not clinically relevant for disease management. Furthermore, use of the Alinity m platform can reduce turnaround time.

Impact of HIV-Related Immune Impairment of Yellow Fever Vaccine Immunogenicity in People Living with HIV-ANRS 12403.

The yellow fever (YF) vaccine is one of the safest and most effective vaccines currently available. Still, its administration in people living with HIV (PLWH) is limited due to safety concerns and a lack of consensus regarding decreased immunogenicity and long-lasting protection for this population. The mechanisms associated with impaired YF vaccine immunogenicity in PLWH are not fully understood, but the general immune deregulation during HIV infection may play an important role. To assess if HIV infection impacts YF vaccine immunogenicity and if markers of immune deregulation could predict lower immunogenicity, we evaluated the association of YF neutralization antibody (NAb) titers with the pre-vaccination frequency of activated and exhausted T cells, levels of pro-inflammatory cytokines, and frequency of T cells, B cells, and monocyte subsets in PLWH and HIV-negative controls. We observed impaired YF vaccine immunogenicity in PLWH with lower titers of YF-NAbs 30 days after vaccination, mainly in individuals with CD4 count <350 cells/mm3. At the baseline, those individuals were characterized by having a higher frequency of activated and exhausted T cells and tissue-like memory B cells. Elevated levels of those markers were also observed in individuals with CD4 count between 500 and 350 cells/mm3. We observed a negative correlation between the pre-vaccination level of CD8+ T cell exhaustion and CD4+ T cell activation with YF-NAb titers at D365 and the pre-vaccination level of IP-10 with YF-NAb titers at D30 and D365. Our results emphasize the impact of immune activation, exhaustion, and inflammation in YF vaccine immunogenicity in PLWH.

Childhood Parental Neglect, Abuse and Rejection Among Transgender Women: A Cross-Sectional Study in Rio de Janeiro, Brazil.

We aimed to estimate the proportions of childhood parental neglect, abuse, and rejection and to evaluate the co-occurrence of these experiences among transgender women in Rio de Janeiro, Brazil. This was a cross-sectional study with a convenience sample enrolled between July 2019 and March 2020, using an adapted version of the Childhood Trauma Questionnaire. Proportions and corresponding confidence intervals (CI) were calculated. Kendall correlation with Tau-b estimator was used in the bivariate analyses. We gathered data from 139 participants. The most prevalent types of childhood traumas were emotional abuse (60.43%, 95% CI [51.79, 68.62]), physical abuse (57.55%, 95% CI [48.90, 65.89]) and sexual abuse (44.60%, 95% CI [36.18, 53.27]). Severe to extreme physical and emotional abuse occurred among 40.29% (95% CI [32.06, 48.93]) and 5.75% (95% CI [2.51, 11.02]) of participants, respectively. The proportion of parental rejection (eviction) was 32.37% (95% CI [25.04, 40.69]) and occurred with the other forms of abuse, except sexual abuse. Multiple types of childhood abuse, neglect, and parental rejection were observed among transgender women in our sample. The harmful effects of childhood abuse on the mental and physical health of people in the transgender population are of concern, particularly considering the cumulative effect produced by the co-occurrence of such events and their harmful lifetime effects. It is urgently necessary to debate and formulate public policies to ensure the right to gender expression from childhood.

SARS-CoV-2 Viral Load in the Nasopharynx at Time of First Infection Among Unvaccinated Individuals: A Secondary Cross-Protocol Analysis of 4 Randomized Trials.

Importance: SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity. Objective: To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease. Design, Setting, and Participants: This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline and acquired COVID-19 during the blinded phase of the trials. The setting included the US, Brazil, South Africa, Colombia, Argentina, Peru, Chile, and Mexico; start dates were July 27, 2020, to December 27, 2020; data cutoff dates were March 26, 2021, to July 30, 2021. Statistical analysis was performed from November 2022 to June 2023. Main Outcomes and Measures: Linear regression was used to assess the association of demographic and clinical characteristics, viral variant, and trial with polymerase chain reaction-measured log10 VL in nasal and/or nasopharyngeal swabs taken at the time of COVID-19 diagnosis. Results: Among 1667 participants studied (886 [53.1%] male; 995 [59.7%] enrolled in the US; mean [SD] age, 46.7 [14.7] years; 204 [12.2%] aged 65 years or older; 196 [11.8%] American Indian or Alaska Native, 150 [9%] Black or African American, 1112 [66.7%] White; 762 [45.7%] Hispanic or Latino), median (IQR) log10 VL at diagnosis was 6.18 (4.66-7.12) log10 copies/mL. Participant characteristics and viral variant explained only 5.9% of the variability in VL. The independent factor with the highest observed differences was trial: Janssen participants had 0.54 log10 copies/mL lower mean VL vs Moderna participants (95% CI, 0.20 to 0.87 log10 copies/mL lower). In the Janssen study, which captured the largest number of COVID-19 events and variants and used the most intensive post-COVID surveillance, neither VL at diagnosis nor averaged over days 1 to 28 post diagnosis was associated with COVID-19 severity. Conclusions and Relevance: In this study of placebo recipients from 4 randomized phase 3 trials, high variability was observed in SARS-CoV-2 VL at the time of COVID-19 diagnosis, and only a fraction was explained by individual participant characteristics or viral variant. These results suggest challenges for future studies of interventions seeking to influence VL and elevates the importance of standardized methods for specimen collection and viral load quantitation.

HPTN 083-02: factors influencing adherence to injectable PrEP and retention in an injectable PrEP study.

INTRODUCTION: HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. METHODS: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non-adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. RESULTS: Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study-related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non-judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection-related anxiety, which abated with time and when given some measure of control (e.g. pre-injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). CONCLUSIONS: Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non-judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective.